Clinical characteristics and outcome of brain abscess Systematic review and meta-analysis
Clinical characteristics and outcome of brain abscess Systematic review and meta-analysis
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DOI：
10.1212/wnl.0000000000000172
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发表时间：
2014-03-04
期刊：
影响因子：
9.9
通讯作者：
van de Beek, Diederik
中科院分区：
文献类型：
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作者：
Brouwer, Matthijs C.;Coutinho, Jonathan M.;van de Beek, Diederik
目的：应用质子磁共振波谱成像(H-1MRSI)技术建立A3243G线粒体DNA突变相关的脑代谢特征，并评价其作为预后生物标志物的可能性。方法：在这项前瞻性队列研究中，我们对135名临床异质性A3243G突变携带者和30名健康志愿者(HV)进行了H-1磁共振成像检查。突变携带者包括45名患有线粒体脑肌病、乳酸酸中毒和卒中样发作(MELAS)的患者；11名在随访期间会发展为MELAS综合征的参与者(转换者)；79名在随访期间不会发展为MELAS综合征的参与者(非转换者)。比较两组的MRSI代谢指标：1)无氧能量代谢(乳酸)，2)神经元完整性(N-乙酰-L-天冬氨酸)，3)线粒体功能(NAA；乳酸)，4)细胞能量(总肌酸)，5)膜生物合成和转换(总胆碱[Tcho])。结果：与以前的研究一致，MELAS患者的乳酸水平(P<；0.001)高于HV患者(P=0.001)，NAA水平低于HV患者。出乎意料的是，与HV相比，转化者表现出更高的NAA(p=0.042)、Tcho(p=0.004)和总肌酸(p=0.002)，以及更高的乳酸水平(p=0.032)。与非转换组相比，转换组的Tcho更高(p=0.015)。在临床上，转换者和非转换者在基线上没有区别。乳酸和Tcho水平是预测个体突变携带者发展MELAS表型风险的可靠生物标志物。结论：对A3243G突变携带者脑代谢的H-1MRSI评估在确定疾病生物标记物和发展为MELAS表型的风险个体方面有希望。
Objective: To establish cerebral metabolic features associated with the A3243G mitochondrial DNA mutation with proton magnetic resonance spectroscopic imaging (H-1 MRSI) and to assess their potential as prognostic biomarkers. Methods: In this prospective cohort study, we investigated 135 clinically heterogeneous A3243G mutation carriers and 30 healthy volunteers (HVs) with H-1 MRSI. Mutation carriers included 45 patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS); 11 participants who would develop the MELAS syndrome during follow-up (converters); and 79 participants who would not develop the MELAS syndrome during follow-up (nonconverters). The groups were compared with respect to MRSI metabolic indices of 1) anaerobic energy metabolism (lactate), 2) neuronal integrity (N-acetyl-l-aspartate [NAA]), 3) mitochondrial function (NAA; lactate), 4) cell energetics (total creatine), and 5) membrane biosynthesis and turnover (total choline [tCho]). Results: Consistent with prior studies, the patients with MELAS had higher lactate (p < 0.001) and lower NAA levels (p = 0.01) than HVs. Unexpectedly, converters showed higher NAA (p = 0.042), tCho (p = 0.004), and total creatine (p = 0.002), in addition to higher lactate levels (p = 0.032), compared with HVs. Compared with nonconverters, converters had higher tCho (p = 0.015). Clinically, converters and nonconverters did not differ at baseline. Lactate and tCho levels were reliable biomarkers for predicting the risk of individual mutation carriers to develop the MELAS phenotype. Conclusions: H-1 MRSI assessment of cerebral metabolism in A3243G mutation carriers shows promise in identifying disease biomarkers as well as individuals at risk of developing the MELAS phenotype.